Antibiofilm properties of 4-hydroxy-3-methyl-2-alkenylquinoline, a novel <i>Burkholderia</i> -derived alkaloid

Biofilms are an important colonization mechanism employed by several microbial species to better establish themselves and monopolize the acquisition of resources across different environs. Some bacteria have evolved specialized metabolites that, when secreted, disrupt the formation and stability of biofilms generated by competing heterospecies, providing the producing organism with an ecological advantage. Soil-derived species are probable candidates for the identification of such compounds, given the intense level of competition that occurs within the terrestrial ecosystem. The MS14 strain of <i>Burkholderia contaminans</i> isolated from soil in Mississippi has previously been shown to produce antimicrobial compounds like occidiofungin and ornibactin. In this report, we demonstrate that this strain also produces 4-hydroxy-3-methyl-2-alkenylquinoline (HMAQ-7), an alkaloid-based metabolite structurally similar to others produced by <i>Burkholderia</i>. HMAQ-7 was isolated and purified in sufficient quantities to enable the elucidation of its covalent structure and the evaluation of its biological effects. The compound was found to possess a unique ability to inhibit biofilm biosynthesis in several species, including opportunistic pathogens like <i>Staphylococcus haemolyticus</i> and within saliva-derived multispecies biofilms. HMAQ-7 also demonstrated an ability to modulate additional cellular behaviors in <i>Bacillus subtilis,</i> including motility and sporulation, suggesting that this molecule is important to the interspecies dynamics present across many diverse microenvironments.IMPORTANCEThe present study furthers our understanding of the structural complexity and the biological functions of the 2-alkyl-4(1H)-quinolone metabolites produced by <i>Burkholderia</i> spp. Low micromolar concentrations of HMAQ-7' induced observable bacterial growth morphology differences. The antibiofilm properties of the HMAQ-7' characterized in this study will promote future investigations into possible biological and applied roles. The ability to alter biofilm formation using HMAQ-7' may facilitate <i>Burkholderia</i> spp. colonization in a multitude of environments, that is, aquatic, soil, and possibly during infection. HMAQ may subvert competition by potential competitor species in natural environments of <i>Burkholderia</i> spp. and possibly lung infections of cystic fibrosis patients.